Background: Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) is a rare autosomal recessively inherited disorder of fatty acid metabolism due to ETFA, ETFB or ETFDH mutations. Molecular defects in the ETFDH gene were found to be responsible for a specific sub-group of patients affected with a variant of the disease responsive to riboflavin. Methods: We report on a man of 69 years complaining of a progressive proximal muscle weakness to the four limbs, associated with muscle pain and elevated CPK (1751 U/L). Results: Histological and biochemical results were strongly suggestive for a defect of fatty acids oxidation. Muscle biopsy showed a lipid storage myopathy. Urinary organic acid analysis showed a marked increase of 2-hydroxyglutaric and ethylmalonic acids excretion and the acylcarnitine profile demonstrated a significant increase of long and medium-chain carnitine esters. An oral therapy of L-carnitine and riboflavin supplementation dramatically improved the clinical picture. Sequence analysis of ETFDH gene showed the presence of a single nucleotide insertion in heterozygous form (c.936insA; p.N313Kfs314X). This insertion causes a frameshift leading to the formation of a truncated protein. Conclusions: Our patient presents clinical, histological and biochemical findings suggestive of MADD even if we failed to find the second causative mutation in ETFDH gene. Moreover, we excluded a copy number gene variation, by probing all the ETFDH exons. We can assume that causative mutations for this gene can act either as a loss of functional protein, when transmitted in autosomal recessive condition or as an aploinsufficient protein when present in one allele only.

Subacute myopathy due to multiple acyl-coenzyme A dehydrogenase deficiency (MADD) in an elderly patient / Pietrini, Vladimiro; Bellanova, Maria Federica; Capozzi, Anna Rita; L., Badiali De Giorgi; G., Cenacchi; C., Gellera. - In: CLINICAL NEUROPATHOLOGY. - ISSN 0722-5091. - 33:3(2014), pp. 231-231.

Subacute myopathy due to multiple acyl-coenzyme A dehydrogenase deficiency (MADD) in an elderly patient

PIETRINI, Vladimiro;BELLANOVA, Maria Federica;CAPOZZI, Anna Rita;
2014-01-01

Abstract

Background: Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) is a rare autosomal recessively inherited disorder of fatty acid metabolism due to ETFA, ETFB or ETFDH mutations. Molecular defects in the ETFDH gene were found to be responsible for a specific sub-group of patients affected with a variant of the disease responsive to riboflavin. Methods: We report on a man of 69 years complaining of a progressive proximal muscle weakness to the four limbs, associated with muscle pain and elevated CPK (1751 U/L). Results: Histological and biochemical results were strongly suggestive for a defect of fatty acids oxidation. Muscle biopsy showed a lipid storage myopathy. Urinary organic acid analysis showed a marked increase of 2-hydroxyglutaric and ethylmalonic acids excretion and the acylcarnitine profile demonstrated a significant increase of long and medium-chain carnitine esters. An oral therapy of L-carnitine and riboflavin supplementation dramatically improved the clinical picture. Sequence analysis of ETFDH gene showed the presence of a single nucleotide insertion in heterozygous form (c.936insA; p.N313Kfs314X). This insertion causes a frameshift leading to the formation of a truncated protein. Conclusions: Our patient presents clinical, histological and biochemical findings suggestive of MADD even if we failed to find the second causative mutation in ETFDH gene. Moreover, we excluded a copy number gene variation, by probing all the ETFDH exons. We can assume that causative mutations for this gene can act either as a loss of functional protein, when transmitted in autosomal recessive condition or as an aploinsufficient protein when present in one allele only.
Subacute myopathy due to multiple acyl-coenzyme A dehydrogenase deficiency (MADD) in an elderly patient / Pietrini, Vladimiro; Bellanova, Maria Federica; Capozzi, Anna Rita; L., Badiali De Giorgi; G., Cenacchi; C., Gellera. - In: CLINICAL NEUROPATHOLOGY. - ISSN 0722-5091. - 33:3(2014), pp. 231-231.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2731105
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